Anthracycline antibiotics including doxorubicin, daunorubicin, and carminomycin have emerged as important chemotherapeutic agents in the treatment of a broad spectrum of neoplastic conditions including acute myloblastic and lymphoblastic leukemias. Doxorubicin (also known as Adriamycin) is the subject of U.S. Pat. No. 3,590,028 and is a prescribed antineoplastic agent used in a number of chemotherapeutic treatments.
The high level of effectiveness and broad spectrum of activity of Adriamycin have lead to numerous efforts to develop anthracycline derivatives which exhibit less toxicity and enhanced activity. Among the derivatives that have been developed and investigated are 4-demethoxyadriamycin, 4-demethoxydaunomycin and certain halogenated derivatives in which the 1- or 2-position in the sugar moiety is substituted by a halogen atom.
2'-Halo derivates of daunomycin, demethoxydaunomycin, doxorubicin and carminomycin are disclosed in U.S. Pat. No. 4,427,664 to Horton et al. U.S. Pat. No. 4,058,519 to Arcamone et al teaches adriamycin derivatives and reactive intermediates, for example, 1-halo-2,3,6-tridoexy-3-fluoroacetamido-4-trifluoroacetoxy-.alpha.-L-lyxo or arabino)hexopyranoses. U.S. Pat. No. 4,046,878 to Patelli et al indicates that the reaction proceeds from daunomycin analogs and uses as a sugar the 1-chloro-2,3,6-trideoxy-3-trifluoroacetamido-4-trifluoroacetoxy-.alpha.-L- lyxo pyranose.